Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor with a slight male
predominance. The tumor has a tendency to arise from deep soft tissue of the trunk
and lower extremities. Rare cases are reported to arise from the mediastinal and retroperitoneal
areas. Its deceptively bland histologic appearance makes this tumor difficult to diagnose.
Also, there are several histologic mimics that may hinder in its diagnosis. We report
a case of low-grade fibromyxoid sarcoma from a 48-year-old woman, first documented
herein to arise from the sigmoid. We also report the value of CD99, BCL2 and MUC4
stains in the diagnosis of this tumor.

Nephrolithiasis is a common kidney disease and one of the major causes of chronic
renal insufficiency. We develop and utilize a glycoxylate induced mouse model of kidney
calcium oxalate crystal deposition for studying the pharmacological effects of fasudil,
a Rho associated protein kinase (ROCK) specific inhibitor, on the kidney injury and
fibrosis caused by calcium oxalate crystallization and deposition. Glycoxylate was
administrated intraperitoneally to C57BL/6J mice for five consecutive days to establish
a mouse model of kidney calcium oxalate crystal formation and deposition. The results
showed that the protein expression levels of E-cad and Pan-ck were lower, and the
protein expression levels of α-SMA and Vim were higher, in the kidney tissue of the
glycoxylate induced model mice compared with the control mice. The changes in protein
expression were weakened when the animals were pretreated with fasudil before glycoxylate
administration. Expression of ROCK, PAI-1, and p-Smad proteins in the kidney tissue
increased in response to glycoxylate treatment, and the increase was eased when the
animals were pretreated with fasudil. Expression of Smad2 and Smad3 in the kidney
tissue remained unchanged after glycoxylate administration. Cell apoptosis and proliferation
in the kidney cortex and medulla were enhanced in response to the glycoxylate induced
calcium oxalate crystal formation and deposition, and fasudil pre-treatment was able
to attenuate the enhancement. The results suggest that Fasudil reduces the glycoxylate
induced kidney calcium crystal formation and deposition and slows down the kidney
fibrogenesis caused by calcium crystal deposition. The possible mechanism may be related
the regulatory effects on Rho/ROCK signal transduction and epithelial-mesenchymal
transition (EMT).

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease more commonly
diagnosed in obesity. Therapeutic options to treat NASH are limited. Liver inflammation
is a hallmark of NASH, and here it was tested whether the lipid mediator resolvin
E1 (RvE1) and chemerin derived C15 peptide, which both exert potent anti-inflammatory
activities, ameliorate NASH pathology. Male mice fed an atherogenic diet for 12weeks,
well described to induce NASH, received intraperitoneal injections of RvE1, C15 peptide
or PBS as control for four days. Both treatments did not affect body weight or serum
ALT. Liver triglycerides were neither reduced by the lipid nor the peptide. Hepatic
expression of the macrophage marker F4/80 and the inflammatory mediators TNF and CCL2
was not changed. Further, fibrotic genes including TGFbeta, alphaSMA and CTGF were
not affected by RvE1 or C15 injections. Serum adiponectin was comparable in the three
groups. RvE1 and C15 are ligands of CMKLR1 whose expression was not reduced upon feeding
the NASH inducing diet. This excludes low receptor levels as reason for therapeutic
failure. In summary, current data demonstrate that RvE1 and chemerin derived C15 peptide
do not ameliorate murine NASH.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has recently been found to suppress experimental
autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Although
its effect was attributed to an anti-inflammatory mechanism, it is not clear whether
this treatment can also directly act on neural cells to promote CNS recovery. The
present study investigates the effect of various concentrations of 1,25(OH)2D3 on
neural stem cell (NSC) proliferation and their differentiation to oligodendrocytes,
the myelinating cells. We have, for the first time, shown that NSCs constitutively
express vitamin D receptor (VDR), which can be upregulated by 1,25(OH)2D3. This vitamin
significantly enhanced proliferation of NSCs, and enhanced their differentiation into
neurons and oligodendrocytes, but not astrocytes. NSCs treated with 1,25(OH)2D3 showed
increased expression of NT-3, BDNF, GDNF and CNTF, important neurotrophic factors
for neural cell survival and differentiation. Overall, we demonstrated that 1,25(OH)2D3
has a direct effect on NSC proliferation, survival, and neuron/oligodendrocyte differentiation,
thus representing a novel mechanism underlying its remyelinating and neuroprotective
effect in MS/EAE therapy.

Much evidence demonstrated that autophagy played an important role in neural inflammation
response after ischemia stroke. However, the specific effect of microglia autophagy
in cerebral ischemia is still unknown. In the current study, we constructed focal
cerebral ischemia model by permanent middle cerebral artery occlusion (pMCAO) in mice.
We detected microglia autophagy and inflammation response in vivo, and observed infarct
brain areas, edema formation, and neurological deficits of mice. We found that pMCAO
induced microglia autophagy and inflammatory response. The suppression of autophagy
using either pharmacologic inhibitor (3-MA) not only decreased the microglia autophagy
and inflammatory response, but also significantly decreased infarct size, edema formation
and neurological deficits in vivo. Taken together, these results suggested that cerebral
ischemia induced microglia autophagy contributed to ischemic neural inflammation and
injury. In addition, our findings also provided novel therapeutic strategy for ischemic
stroke.

Studies of spontaneous mutations in mice have provided valuable disease models and
important insights into the mechanisms of human disease. Ruffled (rul) is a new autosomal
recessive mutation causing abnormal hair coat in mice. The rul allele arose spontaneously
in the RB156Bnr/EiJ inbred mouse strain. In addition to an abnormal coat texture,
we found diffuse epidermal blistering, abnormal electrocardiograms (ECGs), and ventricular
fibrosis in mutant animals. Using high-throughput sequencing (HTS) we found a frameshift
mutation at 38,288,978bp of chromosome 13 in the desmoplakin gene (Dsp). The predicted
mutant protein is truncated at the c-terminus and missing the majority of the plakin
repeat domain. The phenotypes found in Dsp(rul) mice closely model a rare human disorder,
Carvajal-Huerta syndrome. Carvajal-Huerta syndrome (CHS) is a rare cardiocutaneous
disorder that presents in humans with wooly hair, palmoplantar keratoderma and ventricular
cardiomyopathy. CHS results from an autosomal recessive mutation on the 3' end of
desmoplakin (DSP) truncating the full length protein. The Dsp(rul) mouse provides
a new model to investigate the pathogenesis of CHS, as well as the underlying basic
biology of the adhesion molecules coded by the desmosomal genes.

Cancer stem cells (CSCs) are a subset of cancer cells which play a key role in predicting
the biological aggressiveness of cancer due to its ability of self-renewal and multi-lineage
differentiation (stemness). The CSC model is a dynamic one with a functional subpopulation
of cancer cells rather than a stable cell population responsible for tumour regeneration.
Hypotheses regarding the origins of CSCs include (1) malignant transformation of normal
stem cells; (2) mature cancer cell de-differentiation with epithelial-mesenchymal
transition and (3) induced pluripotent cancer cells. Surprisingly, the cancer stem
cell hypothesis originated in the late nineteenth century and the existence of haematopoietic
stem cells was demonstrated a century later, demonstrating that the concept was possible.
In the last decade, CSCs have been identified and isolated in different cancers. The
hallmark traits of CSCs include their heterogeneity, interaction with microenvironments
and plasticity. Understanding these basic concepts of CSCs is important for translational
applications using CSCs in the management of patients with cancer.

Stem cells, upon entering the CNS, can preferentially migrate into disease foci, where
they exert therapeutic effects that compensate for lost tissue, reconstructing damaged
neuronal circuitry and establishing in the brain a new microenvironment suitable for
cell survival. However, the route of stem cell delivery into the CNS remains a challenge:
with systemic administration (e.g., intravenous injection), a fraction of cells may
be trapped in other organs than the CNS, while direct CNS injections, e.g., intracerebroventricular
or transcranial, are invasive. Intranasal (i.n.) delivery of stem cells, in contrast,
can effectively bypass the blood-brain barrier, rapidly enter the CNS, and minimize
systemic distribution. I.n. delivery of stem cells may therefore be a safe and non-invasive
way of targeting the CNS and would thus be a promising therapeutic option for CNS
disease. In this review we discuss the i.n. route for stem cell delivery into the
CNS, and the perspectives of i.n. stem cell-based therapy in CNS disease.